MOLECULAR EPIDEMIOLGOY
Authors: L. Bie, Y. Li, H. Yuan, M. Bondy, M. Bainbridge, S. Jhangiani, A. Jalali, S. E. Plon, G. Armstrong, J. Bernstein, E. Claus, F. Davis, R. Houlston, D. Il'yasova, R. Jenkins, C. Johansen, D. Lachance, R. Lai, C. Lau, R. Merrell, S. Olson, S. Sadetzki, J. Schildkraut, S. Shete, J. Barnholtz-Sloan, M. Wrensch, T. G. Consortium, B. Melin, R. A. Gibbs, C. Haberler, T. Czech, M. Chocholous, C. Dorfer, I. Slavc, S. Hayashi, H. Sasaki, T. Kimura, T. Nakamura, T. Miwa, Y. Hirose, K. Yoshida, A. Jalali, M. Bainbridge, S. Jhangiani, S. E. Plon, G. Armstrong, J. Bernstein, E. Claus, F. Davis, R. Houlston, D. Il'yasova, R. Jenkins, C. Johansen, D. Lachance, R. Lai, C. Lau, R. Merrell, S. H. Olson, S. Sadetzki, J. Schildkraut, S. Shete, J. Barnholtz-Sloan, M. Wrensch, B. Melin, R. A. Gibbs, M. Bondy, R. Jenkins, M. Wrensch, T. Kollmeyer, G. Armstrong, S. Olson, R. Lai, D. Lachance, C. Lau, E. Claus, J. Barnholtz-Sloan, D. Il'yasova, J. Schildkraut, R. Houlston, S. Shete, J. Bernstein, F. Davis, R. Merrell, C. Johansen, S. Sadetzki, T. G. Consortium, B. Melin, M. Bondy, J. Palmer, J. Li, L. Kenyon, D. Andrews, L. Kim, J. Glass, M. Werner-Wasik, W. Shi, S. Takayanagi, A. Mukasa, K. Aihara, K. Saito, R. Otani, S. Tanaka, H. Nakatomi, H. Aburatani, K. Ichimura, K. Ueki, N. Saito, K. M. Walsh, P. A. Decker, J. E. Eckel-Passow, A. M. Molinaro, H. M. Hansen, T. Rice, S. Zheng, T. Kollmeyer, M. S. Berger, S. M. Chang, M. D. Prados, A. Rynearson, A. Caron, M. L. Kosel, D. H. Lachance, B. P. O'Neill, C. Giannini, J. K. Wiencke, R. B. Jenkins, M. R. Wrensch, Z. Wang, Z. Bao, T. Jiang, Z. Wang, Z. Bao, T. Jiang
Journal: Neuro-Oncology (2013)

BACKGROUND: Several studies have observed a change in MGMT silencing and IDH1 mutation in secondary glioblastomas (sGBMs).However, reports about the prognostic value of promoter methylation of the MGMT gene and IDH mutations in sGBMs are few in number.METHODS: The study involved primary and secondary tumor tissue samples from 89 GBMs pts (P/S: 42/47) diagnosed and treated within the First Hospital of Jilin University from Jan 2006 to Nov 2011.After surgical treatment, all GBM pts were subjected to radiotherapy with concomitant administration of TMZ.Pts with GBM were screened for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction (qMSP), and, for IDH mutations by direct sequencing.RESULTS: A total of 42 of 89 pts (47.2%) had primary GBMs (pGBMs) (Group1), while 47 pts (52.8%) had secondary GBMs (Group2).In Group2, 23 pts (21/47, 44.7%) developed a sGBM through progression from a low grade glioma (LGG) WHO grade II and a secondary anaplastic gliomas (sAG) (Group2a), whereas 26 pts (26/47, 55.3%) showed a direct malignant transformation from a LGG to a sGBM (Group2b).MGMT methylation was observed in 38 (42.7%)GBMs, with a higher frequency in sGBMs than pGBMs (24/14, 51.1 vs .33.3%; p ¼ 0.008).MGMT methylation status was associated with increased median survival time in pGBMs and sGBMs pts.IDH1 mutations are present in the majority of sGBMs but rare in pGBMs (31/5, 66.0 vs .11.9%; p , 0.001).Group2a had a higher frequency with IDH1 mutation than group 2b (18/12, 78.3 vs. 46.2%;p , 0.01).The median survival time after malignant progression of all sGBMs pts with an IDH mutation was longer than in pts with wild-type IDH(3.2vs .1.1ys;p , 0.01).IDH1 mutation had an improved outcome in group2a, which is compared with group 2b (3.9ys vs. 2.1ys; p , 0.05).CONCLUSIONS: In our population, pts with sGBM and IDH mutation had a significantly improved outcome.In addition, MGMT methylation is also a powerful prognostic marker in sGBM pts.